Acute decompensated heart failure (ADHF) is the largest cause of hospitalization in the United States among patients 65 and older. See Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009; 119(3):e21-e181 incorporated herein by this reference. These patients often enter the emergency room with significant volumes of excess fluid and a number of complications due to this excess fluid. Complications can include dyspnea, orthopnea, peripheral edema, and pulmonary edema.
Current treatment for these patients is to administer a number of doses of a diuretic to increate urination to enable the patient to lose the excess fluid. This therapy can take a number of days while the patient requires vigilant monitoring in an intensive care unit.
A recent study that attempted to determine the ideal diuretic dose for ADHF patients demonstrated how poorly patients fare with the current therapy. Across all treatment groups, 42% of patients enrolled in the trial died, were re-hospitalized, or had an emergency department visit within 60 days of treatment. See Felker G M, Lee K L, Bull D A, et al. Diuretic Strategies in Patients with Acute Decompensated Heart Failure (DOSE). The New England Journal of Medicine, 2011; 364(9):797-805 incorporated herein by this reference.
There are a number of factors that contribute to the poor prognosis of these patients. Patients with ADHF often have a number of co-morbidities, complicating their treatment and giving them a poor prognosis. These patients are often already taking a diuretic chronically, which lessens the impact of the diuretics when they are administered during their hospitalization. This also contributes to the fact that patient response to diuretics is unpredictable. Some patients may begin diuresis immediately after diuretic injection, others may require additional doses to induce diuresis.
A paradox of the ADHF patient involves the fact that while these patients may have 40 additional liters of fluid in their body, they may be intravascularly dehydrated. The extra fluid may be contained within the patient's cells and in the extra-cellular space (“third space”). The injection of diuretics then only causes fluid to be lost from the already depleted intravasculature. This can lead to a condition known as “diuretic resistance”, wherein the patient's kidney attempts to retain the fluid lost after the initial doses of diuretic and fails to respond to increasing doses of diuretic. As fluid retention increases, the patient's urine output can drop to zero. Once the patient fails to respond to diuretics, treatment becomes very difficult. One of the ways ADHF kills patients is by retaining so much fluid that the fluid begins to build up in the patient's lungs, eventually causing pulmonary edema and eventually causing the lungs to fail. Diuretics are the most common method used to remove that excess fluid and prevent pulmonary edema. If diuretics fail to induce urine output due to diuretic resistance, the clinician loses an effective tool for protecting the patient from pulmonary edema.
The intravascular depletion caused by diuretic therapy can also reduce blood supply to the kidney, causing additional damage to the kidney.
Ultrafiltration therapy has been studied as a potential method for removing fluid from patients at risk of diuretic resistance. The therapy requires a pump that removes blood from the patient and passes the blood through a filter. The filter has small holes that allow fluid and electrolytes to be removed from the blood, but does not pass red blood cells or proteins. The blood is then returned to the body with some portion of the fluid and electrolytes removed. Ultrafiltration can be performed using a dialysis machine or a dedicated device, such as the Aquadex (Gambro, Brooklyn Park, Minn.).
While a number of studies have demonstrated that Ultrafiltration can effectively remove fluid from ADHF patients, one of the largest studies of the therapy to date has found that Ultrafiltration may lead to more kidney damage than diuretic therapy. See Bart B A, Goldsmith S R, Lee K L, et al. Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome, The New England Journal of Medicine, 2012; 367(24):2296-304 incorporated herein by this reference.
Hypertonic saline I.V. may be an effective in medical management of cerebral (brain) edema and elevated intracranial pressure (ICP). It is a critical component of perioperative care in neurosurgical practice. Traumatic brain injury (TBI), arterial infarction, venous hypertension/infarction, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), tumor progression, and postoperative edema can all generate clinical situations in which ICP management is a critical determinant of patient outcomes. Use of hypertonic saline and other osmotic agents is among the most fundamental tools to control ICP. Recently several scientific papers taught the counterintuitive use of hypertonic saline to treat congestive heart failure (CHF or simply heart failure) patients with fluid overload resistive to diuretics. CHF patients retain salt and water to maintain blood pressure and their salt intake is severely limited by the traditional therapy paradigm.
Patema S, Di Pasquale P, Parrinello G, et al. in “Changes in brain natriuretic peptide levels and bioelectrical impedance measurements after treatment with high-dose furosemide and hypertonic saline solution versus high-dose of furosemide alone in refractory congestive heart failure: a double-blind study” (7 Am Coll Cardiol 2005; 45:1997-2003; further called Patena Paper) and Stevenson et al. in JACC Vol. 45, No. 12, 2005 Editorial Comment on the Patena Paper describe and comment on results from the randomized study of 94 patients hospitalized with clinical volume overload. The study suggests that the administration of sodium may paradoxically treat the sodium-retaining state. For acute diuresis, very high doses of loop diuretic furosemide (500 to 1,000 mg) were administered twice daily with either hypertonic saline or vehicle infusion concomitantly. Patients receiving hypertonic saline had greater volume loss and were discharged sooner, with better renal function and higher serum sodium.
According to Stevenson, the mechanisms by which in the acute phase of CHF the I.V. infusion of excess saline load facilitated diuresis are open to interpretation and complex. Unmistakably though, there was a larger amount of free water diuresis in the hypertonic saline group. This may relate in part to an acute osmotic effect of hypertonic saline to increase mobilization of extravascular fluid into the central circulation and renal circulation. Direct intratubular effects of sodium flooding may overwhelm the postdiuretic NaCl retention and over time may reduce the diuretic “braking” phenomenon by which fluid escaping past the ascending limb is captured downstream. Neurohormone levels may have been suppressed by hypertonic saline. Both increased intravascular volume and greater delivery of sodium to the distal tubule should inhibit the rennin-angiotensin-aldosterone system Inhibition of aldosterone release could explain the lower relative potassium excretion in the high sodium group, Reduction in angiotensin II levels could lead also to a decrease in antidiuretic hormone (ADH) vasopressin release despite temporary increase in serum osmolarity. There may also be a small contribution of increased intravascular volume to stimulation of the low-pressure and high-pressure baroreceptors that inhibit vasopressin release. Decreased levels of vasopressin could reduce the aquaporin channels through which water is reabsorbed, leading to the greater free water excretion observed. Reduced vasopressin also might also decrease compensatory over-expression of the sodium transporter in the ascending limb, which diminishes diuretic effect.